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Phenylketonuria (PKU)


Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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Phenylketonuria is a disorder of amino acid metabolism that occurs in infants born without the ability to normally break down an amino acid called phenylalanine. Phenylalanine, which is toxic to the brain, builds up in the blood. Phenylketonuria occurs when parents pass the defective gene that causes this disorder on to their children.

  • Phenylketonuria is caused by a lack of the enzyme needed to convert phenylalanine to tyrosine.

  • Symptoms include intellectual disability, seizures, nausea, vomiting, an eczema-like rash, and a mousy or musty body odor.

  • The diagnosis is based on a blood test.

  • Children who are diagnosed and treated early should develop normally.

  • A strict phenylalanine-restricted diet allows for normal growth and development.

Amino acids are the building blocks of proteins and have many functions in the body. Phenylketonuria (PKU) is a disorder that causes a buildup of the amino acid phenylalanine, which is an essential amino acid (one that cannot be made in the body but must be consumed in food). Excess phenylalanine is normally converted to tyrosine, another amino acid, and eliminated from the body. Without the enzyme that converts it to tyrosine, called phenylalanine hydroxylase, phenylalanine builds up in the blood and is toxic to the brain, causing intellectual disability.

There are different types of inherited disorders. In PKU, both parents of the affected child carry a copy of the abnormal gene. Because usually two copies of the abnormal gene are necessary for the disorder to occur, usually neither parent has the disorder. (See also Overview of Hereditary Metabolic Disorders.)

Symptoms of PKU

Newborns with PKU rarely have symptoms right away, although sometimes they are sleepy or eat poorly. Symptoms develop slowly over several months as phenylalanine builds up in the blood. If not treated, affected infants progressively develop intellectual disability over the first few years of life, which eventually becomes severe. Other symptoms include

  • Seizures

  • Nausea and vomiting

  • Eczema-like rash

  • Lighter skin, eye, and hair color than their family members

  • Aggressive or self-injurious behavior

  • Hyperactivity

  • Sometimes psychiatric symptoms

Untreated children with phenylketonuria often give off a mousy or musty body odor in their urine and sweat. This odor is the result of phenylacetic acid, which is a by-product of phenylalanine.

Diagnosis of PKU

  • Newborn screening test

  • Prenatal screening tests

Phenylketonuria is usually diagnosed with a routine newborn screening test.

PKU occurs in most ethnic groups. If PKU runs in the family and DNA is available from an affected family member, the prenatal screening tests amniocentesis or chorionic villus sampling with analysis of DNA (the building blocks of genes) can be done to determine whether a fetus has the disorder.

Parents and siblings of children with PKU can be tested to find out whether they carry the gene that causes the disease. If two carriers conceive a child, that child has a 1 in 4 chance of being born with the disease. Carriers are people who have an abnormal gene for a disorder but who do not have symptoms or visible evidence of the disorder.

Prognosis of PKU

Children who are treated in the first few days of life do not develop the severe symptoms of phenylketonuria. A phenylalanine-restricted diet, if started early and maintained well, allows for mostly normal development. However, even with very good control of the diet, affected children still may develop mild mental health problems and may have difficulties in school. Dietary restrictions started after 2 to 3 years of age may control extreme hyperactivity and seizures and raise the child’s eventual intelligence quotient (IQ) but do not reverse intellectual disability. Recent evidence suggests that some intellectually disabled adults with PKU (born before newborn screening tests were available) may function better when they follow the PKU diet.

A phenylalanine-restricted diet should continue for life, or intelligence may decrease and neurologic and mental problems may ensue.

Children who are born to mothers who have poorly controlled PKU (that is, they have high phenylalanine levels) during pregnancy are at high risk of developing an abnormally small head (microcephaly) and developmental problems. This condition is called maternal PKU.

Prevention and Treatment of PKU

  • Phenylalanine-restricted diet

To prevent intellectual disability, people must restrict phenylalanine intake (but not eliminate it altogether because people need some phenylalanine to live) beginning in the first few weeks of life. Because all natural sources of protein contain too much phenylalanine for children with PKU, affected children cannot have meat, milk, or other common foods that contain protein. Instead, they must eat a variety of products that are specially manufactured to be phenylalanine-free. Low-protein natural foods, such as fruits, vegetables, and restricted amounts of certain grain cereals, can be eaten.

Special nutritional products, including infant formula without phenylalanine, are also available. Examples of these special products include PKU Anamix®, XPhe Maxamaid®, and XPhe Maxamum®; Phenex®-1 and Phenex®-2; Phenyl-Free® 1 and Phenyl-Free® 2; pku 1, pku 2, and pku 3; PhenylAde® (varieties); PKU Lophlex® LQ; and Phlexy-10®.

Women who have PKU and who are planning on becoming pregnant should follow the recommended diet and keep their PKU under control.

Doctors may give supplements of the amino acid tyrosine and a drug called sapropterin. This drug helps increase a person's tolerance of phenylalanine.

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